Affiliation

Abstract

Smoking influences body weight such that smokers weigh less than non-smokers and smoking cessation often leads to weight increase. The relationship between body weight and smoking is partly explained by the effect of nicotine on appetite and metabolism. However, the brain reward system is involved in the control of the intake of both food and tobacco. We evaluated the effect of single-nucleotide polymorphisms (SNPs) affecting body mass index (BMI) on smoking behavior, and tested the 32 SNPs identified in a meta-analysis for association with two smoking phenotypes, smoking initiation (SI) and the number of cigarettes smoked per day (CPD) in an Icelandic sample (N=34,216 smokers). Combined according to their effect on BMI, the SNPs correlate with both SI (r=0.019, P=0.00054) and CPD (r=0.032, P=8.0 × 10(-7)). These findings replicate in a second large data set (N=127,274, thereof 76,242 smokers) for both SI (P=1.2 × 10(-5)) and CPD (P=9.3 × 10(-5)). Notably, the variant most strongly associated with BMI (rs1558902-A in FTO) did not associate with smoking behavior. The association with smoking behavior is not due to the effect of the SNPs on BMI. Our results strongly point to a common biological basis of the regulation of our appetite for tobacco and food, and thus the vulnerability to nicotine addiction and obesity.

Figures

Figure 1

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Association of obesity variants with…

Figure 1

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Association of obesity variants with smoking initiation (SI) and CPD. The effects on…

Figure 1

Association of obesity variants with smoking initiation (SI) and CPD. The effects on smoking behaviors are depicted vs the effects on BMI from a large meta-analysis. (a) The effect on smoking initiation vs the effect on BMI. (b) The effect on CPD vs the effect on BMI. The BMI effect is in standard units, and the effects on SI and CPD were obtained using a standard fixed-effects additive meta-analysis to combine the results for each SNP from Iceland with additional data from three large GWAS., , The effects on SI are the β-values from logistic regression treating ever smoking as the response and the allele counts as covariates, and the GWAS of CPD used smoking quantity in categories with each category representing 10 CPD (effect size of 0.1=1 CPD). The dots representing each data point are color coded to indicate the p-value obtained as red (P<0.0001), yellow (P<0.001), green (P<0.05) and black (P≥0.05) and the input data are provided in (Supplementary Table 1).